Chapter 73. Chronic Kidney Disease Mineral Bone Disorder (CKD‐MBD)

Hruska, Keith A.; Mathew, Suresh

doi:10.1002/9780470623992.ch73

Cited by 14 publications

(12 citation statements)

References 37 publications

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“…Factors implicated in this disorder include increased plasma calcium; vitamin D toxicity; and altered growth factors and cytokines such as BMP, TGF-β and IGF-1, and IL-6. These are only a few components of what is a poorly understood multifactorial pathogenesis (148, 149). …”

Section: Renal Osteodystrophymentioning

confidence: 99%

“…For high-turnover disease, therapy is focused on phosphorus restriction or use of phosphate binders, correcting vitamin D deficiency, and the occasional use of calcium supplements. Calcimimetic agents that bind to the parathyroid-gland plasmamembrane Ca 2+ receptor were recently used to inhibit PTH secretion (149). In contrast, low-turnover disease is managed primarily by methods designed to increase PTH levels.…”

Section: Renal Osteodystrophymentioning

confidence: 99%

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Disorders of Bone Remodeling

McDonald

2011

Annu. Rev. Pathol. Mech. Dis.

1,032

842

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The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms.

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Section: Renal Osteodystrophymentioning

confidence: 99%

Section: Renal Osteodystrophymentioning

confidence: 99%

Disorders of Bone Remodeling

McDonald

2011

Annu. Rev. Pathol. Mech. Dis.

1,032

842

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“…In patients with chronic kidney disease (CKD), calcitriol deficiency worsens with declining renal function as a result of glomerular loss [24, 25]. Deficiency of 25-OHD is also common among patients with CKD [13, 14, 25], and lower levels are associated with poorer kidney function [26].…”

Section: Vitamin D Deficiency In Organ Transplant Candidatesmentioning

confidence: 99%

Vitamin D in organ transplantation

Stein

Shane

2011

Osteoporos Int

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Vitamin D deficiency is prevalent among patients with end-stage organ failure awaiting transplant. Low serum 25-hydroxyvitamin D (25-OHD) levels in these patients may be related to many disease-specific factors, as well as decreased sunlight exposure and limited intake of foods containing vitamin D. Low serum 25-OHD levels are also extremely common following solid organ transplantation, both during the immediate postoperative period and in long-term graft recipients. Demographic and lifestyle factors are important in determining D status in transplant recipients. Worse vitamin D status is associated with poorer general health, lower albumin, and even decreased survival among these patients. Although several studies have demonstrated that active forms of vitamin D and its analogues prevent bone loss following transplantation, the data do not show consistent benefit. These therapies may have particular utility after renal transplantation. However, given the narrow therapeutic window with respect to hypercalcemia and hypercalciuria, and the demonstrated efficacy of bisphosphonates to prevent post-transplantation bone loss, we regard these agents as adjunctive rather than primary therapy for transplantation osteoporosis. The effects of 1,25(OH)2D on the immune system, which are still being elucidated, may have potential for reducing infections and preventing allograft rejection after transplantation.

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“…1 Following the naming of the CKD-MBD syndrome, 2 it became apparent that the syndrome had an earlier onset in the course of kidney disease than the hyperparathyroidism and calcitriol deficiency that had previously been linked to renal osteodystrophy. 3,4 Characterization of CKD-MBD in early CKD demonstrated onset in stage 2 CKD both clinically and in translational models. 4–8 In early CKD, the CKD-MBD was characterized by arterial vascular cell dedifferentiation/calcification, loss of klotho, increased fibroblast growth factor 23 (FGF-23) secretion, and an osteodystrophy.…”

mentioning

confidence: 99%

Ligand trap of the activin receptor type IIA inhibits osteoclast stimulation of bone remodeling in diabetic mice with chronic kidney disease

Sugatani¹,

Agapova²,

Fang³

et al. 2017

Kidney International

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Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr−/− high fat-fed mouse model of atherosclerotic vascular calcification and diabetes. Twenty mice with CKD, hyperphosphatemia, hyperparathyroidism, and elevated activin A were treated with RAP-011, wherease 19 mice were given vehicle twice weekly from week 22 until the mice were killed at 28 weeks of age. The animals were then evaluated by skeletal histomorphometry, micro-computed tomography, mechanical strength testing, and ex vivo bone cell culture. Results in the CKD groups were compared with those of the 16 sham-operated ldlr−/− high fat-fed mice. Sham-operated mice had low-turnover osteodystrophy and skeletal frailty. CKD stimulated bone remodeling with significant increases in osteoclast and osteoblast numbers and bone resorption. Compared with mice with CKD and sham-operated mice, RAP-011 treatment eliminated the CKD-induced increase in these histomorphometric parameters and increased trabecular bone fraction. RAP-011 significantly increased cortical bone area and thickness. Activin A-enhanced osteoclastogenesis was mediated through p-Smad2 association with c-fos and activation of nuclear factor of activated T cells c1 (NFATc1). Thus, an ActRIIA ligand trap reversed CKD-stimulated bone remodeling, likely through inhibition of activin-A induced osteoclastogenesis.

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Chapter 73. Chronic Kidney Disease Mineral Bone Disorder (CKD‐MBD)

Cited by 14 publications

References 37 publications

Disorders of Bone Remodeling

Disorders of Bone Remodeling

Vitamin D in organ transplantation

Ligand trap of the activin receptor type IIA inhibits osteoclast stimulation of bone remodeling in diabetic mice with chronic kidney disease

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